• Journal of Pharmaceutical Investigation
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• 제30권4호
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• pp.273-278
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• 2000

Several topical preparations containing lidocaine, a widely used local anesthetic agent, have been developed and marketed recently for the treatment of premature ejaculation. In this study, microemulsion(ME)-based hydrogels containing lidocaine were prepared by dispersing ME to hydrogel bases such as Carbopol, sod. alginate, and sod. carboxymethylcellulose. Lidocaine-containing ME was thermodynamically stable over 6 months and had a diameter ranging from 10 to 100 nm. In vitro skin penetration of lidocaine from ME-based hydrogels followed apparent zero-order kinetics. ME-based hydrogel showed higher drug penetration during fifteen minutes after application than alcoholic hydrogel, reference preparation. Tail flick test in rat was introduced to compare in vivo local anesthetic effects of different hydrogels, and the results showed that ME-based hydrogels are superior to other hydrogels. In optical microscopy, recrystallization of lidocaine was observed within 5 min after application of reference hydrogel, but there was no change in ME-based hydrogels even after 30 minnute. These results indicated that ME-based hydrogels had some advantages in skin penetration, anesthetic effect and physical stability compared with alcoholic hydrogels. Finally it is possible to conclude that ME-based hydrogels containing lidocaine is a good topical drug delivery system for the treatment of premature ejaculation.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.1-8
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• 1993

A simple and quick method based on the transient diffusion theory for predicting the steady state rate of penetration of a drug after transdermal drug administration was proposed. The amount of drug entering the stratum corneum was determined by 20 strippings with an adhesive tape. From the profile of the amount of drug as a function of the number of strippings, the quantity of drug on the surface of stratum corneum was extrapolated. Based on the amounts of drug entering the stratum corneum during two time intervals $(t_1\;and\;t_2)$ within 1 hour after the application, the diffusion and partition coefficient were determined. Once the diffusion coefficient of the drug in the stratum corneum and the partition coefficient (stratum corneum/vehicle) were determined from the present approach, the steady-state flux of penetration across the stratum corneum was calculated. The steady-state rates of penetration of ascorbic acid and estradiol across hairless mouse skin were evaluated from this approach and compared with those obtained from ill vitro penetration experiment using excised hairless mouse skin. The data confirmed that the proposed method can predict the steady-state rate of penetration of these drugs across the stratum corneum.

• 약학회지
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• 제40권2호
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• pp.155-162
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• 1996

Hyperkeratinization is a dermatologic disorder, which is due to the increase of corneocyte cohesion force. Glycolic acid, an alpha hydroxy acid(AHA), has been used to breakdown the hyperkeratinization processes. However, it has a problem of skin irritation when applied topically, due to the strong acidity especially in high concentration. A molecular optimization of glycolic acid has been tried to reduce the skin irritation by the way of prodrug formation. Ethyl glycolate was synthesized by the esterification of glycolic acid with ethanol in acidic conditions in the presence of sulfuric acid, and examined under the spectroscopic trials, such as UV, IR, $^1H$-NMR, and GC-MS. The physicochemical and biopharmaceutical properties of the prodrug were also evaluated. Through the toxicological tests of both skin irritation and eye mucous irritation, it has been proved that ethyl glycolate was less irritant than glycolic acid, since the pH value of synthetic prodrug was higher than that of glycolic acid. In the penetration test through nude mouse skin by diffusion cell, ethyl glycolate was continuously hydrolyzed to glycolic acid, which was assayed form the receptor compartment. It was obtained that the penetrated amount of ethyl glycolate was five times higher than that of glycolic acid. These results suggest that ethyl glycolate might be a successful prodrug of glycolic acid to reduce the skin irritation and to increase the skin penetration as well.

• 대한화장품학회지
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• 제49권2호
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• pp.127-139
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• 2023

본 연구에서는 의약품 원료로 잘 알려진 minoxidil과 화장품 원료인 diaminopyrimidine oxide (DAO) 활성성분으로 사용하여 니오좀(niosome)의 물성평가와 더불어 인공피부에 대한 경피투과율을 비교하였다. 나노입자의 니오좀을 제조하기 위해 고압유화(high pressure homogenization) 방법을 이용하였으며 제타사이저(zetasizer)로 물성평가를 진행하였다. 활성성분을 포함한 니오좀의 입자크기는 HLB에 따라 평균 99 ~ 123 nm, 제타전위(zeta potential)는 -60 ~ -81 mV의 범위로 측정되었다. DSC (differential scanning colorimetry)를 통해 결정성 성분인 minoxidil이 니오좀 내에 무결정 상태로 균일하게 용해되어 있음을 확인하였다. 경피투과량을 확인 및 비교하기 위해 in vitro Franz diffusion cell 방법으로 측정하였으며, 니오좀 제형이 대조군인겔 제형보다 minoxidil의 경우 3.4배, DAO의 경우 11.1배 높은 투과율을 보였다. 또한 minoxidil과 DAO 니오좀의 경피투과 비교 시 유사한 경향을 보였으며, 상대적으로 DAO의 투과량이 많았다. HLB 값을 달리한 니오좀 제형을 Cryo-TEM을 이용하여 형상을 관찰하였으며, 모두 소포체가 형성되었으며 SUV (small unilamella vesicle)와 LUV (large unilamella vesicle)의 중간 형태임을 확인하였다. 본 연구를 통하여 탈모에 효과적인 약물인 minoxidil과 화장품 원료인 DAO 성분을 니오좀 제형에 캡슐화시킴으로써 효과적으로 피부에의 전달을 기대할 수 있다.

• 약학회지
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• 제45권5호
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• pp.506-512
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• 2001

Ketoprofen (KP) was formulated as a transdermal patch using the percutaneous penetration enhancers sorbitan monmmleate(SMO), polyvinylpyrrolidone(PVP). The control patch without penetration enhancers showed a KP flux of 8.9$\pm$0.75$\mu\textrm{g}$/$\textrm{cm}^2$/h The flux was increased in proportion to the concentration of SMO added. Furthermore, lag times were decreased upon addition of SMO. Conversely; the skin flux of KP was decreased in proportion to the concentration of PVP added. Pharmacokinetic parameters including $C_{max}$, $T_{max}$, and AUC were increased when SMO was added. However, $C_{mas}$ significantly decreased by the addition of PVP. $T_{max}$ was not significantly different in 2%, 4%, and 8% PVP patches. Patches containing 4% PVP showed the highest AUC value (19.158$\mu\textrm{g}$.h/ml). We found that the effectiveness of the two percutaneous penetration enhancers for topical KP patches was similar, with the addition of appropriate amounts of HPC modifying both skin flux and lag time of KP in the patches. In conclusion, it is possible to manufacture KP patches exhibiting high AUC, high skin flux, and short lag time using percutaneous penetration enhancers of SMO and PVP.

• 한국근적외분광분석학회:학술대회논문집
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• 한국근적외분광분석학회 2001년도 NIR-2001
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• pp.3101-3101
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• 2001

Near Infrared spectroscopy (NIR) used on human skin measurement was explored in the past decade. Many publications in different journals and magazines discussed the feasibility of the NIR technique for cosmetic product property studies. Based upon the results of pioneers, we have pursued some work of the NIR instrument coupled with a probe module for skin measurement in vivo and vitro. In part I of this paper, the specific Near Infrared spectroscopy instrument stability, human subject conditions and other parameters, which could affect the measurements reproducibility are discussed. Second derivative NIR spectra and Principle Components Analysis (PCA) are utilised for data interpretation. In part II of this paper, the relationship of human skin moisture and ageing, the gender information and finally, the discovery of penetration depth of NIR incident light on skin are reported. A theoretical penetration depth calculation equation is proposed. In part III, the study results of a couple of commercial skin care products effect will be described. The skin lotions were applied on human skin (in vivo) in order to exam the NIR feasibility to monitor the changes of moisture level. The results are consistently positive. From our primary study, it can conclude that the NIR is potentially a very powerful instrument for skin condition diagnostics, either for cosmetic and/or for medication purposes.

• 대한화장품학회지
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• 제47권2호
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• pp.179-184
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• 2021

각질층은 피부의 가장 바깥쪽에 위치하여 피부 내 수분을 유지시킨다. 피부 보습은 각질층 내 천연보습인자(natural moisturizing factors, NMF)에 의존하는데, NMF 중 아미노산이 가장 많은 비율을 차지한다. 본 연구에서는 NMF 중 serine (Ser)의 피부 투과율을 개선시키기 위해 생체 적합한 고형지질인 stearic acid 기반 고형지질나노입자(solid lipid nanoparticles, SLNs)를 설계하였다. Ser 봉입 SLNs은 이중 가온용융유화법으로 제조하였다. 평균 입자 크기는 256.30 ~ 416.93 nm이었고 제타전위는 -17.60 ~ -35.27 mV이었다. 유화제의 지용성 또는 친수성의 정도가 각각 높아질수록 입자크기 작아지고 안정성 및 봉입율이 높아지는 경향을 보였다. Ser의 피부 투과 연구를 위해 인체 표피 유래 피부 조직(SkinEthic^TM RHE)을 사용하였다. Ser의 피부 투과결과 SLN을 적용한 제형이 대조군인 Ser 용액에 비해 약 4.1 ~ 6.2 배 투과율이 개선되었음을 확인하였다. 유화제의 지용성 또는 친수성의 정도가 각각 높아질수록 Ser의 피부 투과율이 높아지는 경향을 보였다. 따라서, Ser이 봉입된 SLN은 기능성화장품의 보습효과 처방을 위한 경피흡수 제형으로 사용될 수 있을 것으로 기대된다.

• Journal of Pharmaceutical Investigation
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• 제31권2호
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• pp.107-112
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• 2001

In order to reduce the systemic side effects and gastrointestinal irritation after its oral adminitration, ketoprofen was formulated as water-soluble packs. The effects of fatty acids and fatty alcohols on the penetration of ketoprofen through excised rat skins were evaluated. The role of stratum corneum as a protective barrier was also investigated. Fatty acids and fatty alcohols were generally effective in promoting ketoprofen penetration. The flux of ketoprofen through rat skin was maximized when oleic acid or lauryl alcohol was used as an enhancer. As the concentration of fatty acids and fatty alcohols varied from 0% to 10%, the amounts of ketoprofen penetrated were in direct proportion to that of fatty acids but those had no relationship with that of fatty alcohols. The penetration of ketoprofen through stripped skin was enhanced compared to normal skin irrespective of enhancer type, which indicated that the action site of enhancers would be stratum corneum.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.357-363
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• 1997

The effects of formulation variables of topical lotion on the skin permeation of ketoprofen were evaluated using excised rat skins. The formulation variables were the amounts of poloxamer 407, drug and ethanol, and penetration enhancers. The Keshary-Chien diffusion cells were used for the diffusion study. The flux of ketoprofen linearly decreased as the concentration of poloxamer increased from 5% to 15% in the preparation, and linearly increased as the amount of drug increased. Penetration enhancers such as fatty acids and fatty alcohols showed markedly enhancing effects at the level of 5%. Among them, the highest flux was shown in linolenic acid. From these results, optimum formula containing 3% ketoprofen, 5% poloxamer 407, 40% ethanol and 5% linolenic acid having the flux of 537.6 $\mu$g/$\textrm{cm}^2$/hr were noted.

• 한국응용과학기술학회지
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• 제24권4호
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• pp.410-415
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• 2007

Functional cosmetics are intensively investigated for the effectiveness of skin whitening, anti-aging and slimming. For enhancing the effectiveness, active ingredients should be delivered into the cell in the dermis. The amounts of penetration of caffeine and $Arbutin^{(R)}$ were tested, in vitro, using Franz diffusion cell. Oil-in-water emulsions were used for the vehicles of the transport. For the measuring the amounts of active ingredients delivered into the dermal skin, tape stripping was done after finishing the penetration experiments. The amounts of delivered caffeine were $8.45{\pm}$ 1.26ug/ml before tape stripping and $3.45{\pm}$ 1.80ug/ml after tape stripping, however, the amounts of delivered $Arbutin^{(R)}$ was quite small to detect. From now on, proper vehicles are considered for enhancing the delivery of $Arbutin^{(R)}$ Hairless mouse skin was compared with pig skin as a transdermal delivery membrane. The aspects of delivery were similar, but the amount of delivered ingredients using pig skin was larger than that of using hairless mouse skin. Therefore, the pig skin would be considered as a membrane for drug delivery experiments.